The paper identifies the level of the phospholipid PI4P as the link between inactivation of Patched by Hedgehog binding, and trafficking of Smoothened to the plasma membrane, leading to its activation. In a series of elegant epistasis studies in Drosophila, the authors show that the level of PI4P, which is determined by the balance between the phospholipid kinase STT4 and phosphatase Sac1, mediates the activation of the Hedgehog...

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